Adhesion formation is a major post-surgical complication with no practical solution. The incidence of adhesion formation following surgery approaches 100 per cent, according to some sources, with a clinically significant complication rate of about 5 to 10 per cent, depending on the type of surgery. Among such complications are bowel obstruction, infertility, and pain. Occasionally, adhesions necessitate a second operative procedure to remove the adhesion, which may in turn further aggravate the problem.
Because of the seriousness of the problem, much medical research has been performed in efforts to find ways to combat adhesions. See, for instance, Stangel et al., "Formation and Prevention of Postoperative Abdominal Adhesions", the Journal of Reproductive Medicine,, Vol. 29, No. 3, Mar. 1984 (pages 143-156), and diZerega, "The Cause and Prevention of Postsurgical Adhesions", published by Pregnancy Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 18, Room 101, Bethesda, Md. 20205. Among the approaches that have been tried for preventing post-surgical adhesion are the following:
Systemic administration of ibuprofen (e.g., see Singer, U.S. Pat. No. 4,346,108);
Parenteral administration of antihistamines, corticosteroids, and antibiotics;
Intraperitoneal administration of dextran solution and of polyvinylpyrrolidone solution; and
Systemic administration of oxyphenbutazone, a non-steroidal anti-inflammatory drug that acts by inhibiting prostaglandin production.
Corticosteroids have been administered intraperitoneally as well as systemically in efforts to prevent adhesions. (See the Stangel et al. article, cited above, on page 147, as well as the articles cited therein.) Some studies have questioned the efficacy of corticosteroids in adhesion prevention. In high doses, these materials may suppress the immune system and interfere with wound healing. Therefore, the use of corticosteroids does not seem to be an acceptable solution to the post-operative adhesion problem.
On the basis of the results of animal studies and limited human clinical studies, the systemic administration of non-steroidal anti-inflammatory agents such as ibuprofen (usually in combination with other medicaments such as antibiotics) appears to be the most efficacious pharmacological means now known to reduce the incidence of Post-surgical adhesions. An objection to this means is that relatively large amounts of the drug must be administered over a period of several days, thereby subjecting the patient to the significant risk of experiencing adverse side effects. Also, this means has been shown to be effective only in a limited number of types of surgical procedures, e.g., gynecological surgery. As reported by Nishimura, Nakamura, and diZerega (Journal of Surgical Research 36, 115-124, Feb. 1984), the minimum effective dose of systemically administered ibuprofen to inhibit postsurgical adhesion formation after abrasion or ischemia of the uterine horn of rabbits, is 70 mg/kg/day, administered once a day for at least 3 and preferably for 5 days post-operatively, with an additional dose 1 hour before surgery. In a similar series of experiments, Siegler et al. (Fertility and Sterility 34. No. 1, Jul. 1980, pages 46-49) found an effective dose of systemically administered ibuprofen to be about 21 mg/kg/day, administered three times daily (in three 7 mg/kg doses) for two days post-operatively, with the initial injection being given 30 minutes before surgery. The authors also reported that the best results were found in two rabbits that were each inadvertently given three extra 7 mg/kg doses. In order to deter adhesion formation in surgery to try to cure infertility, Corson et al. (The Journal of Reproductive Medicine, Vol. 29, No. 3, pages 143-156, Mar. 1984) recommend a regimen including systemically administered ibuprofen, 400 mg per dose three to four doses per day, starting the night of surgery and continuing to the fifth postoperative day. Assuming that the average woman weighs about 48 kg (110 pounds), this is a recommended dosage of 25 to 33 mg/kg/day. Singer, in U.S. Pat. No. 4,346,108, recommends a dosage of from about 2.5 to 50 mg/kg/day in single or divided doses, for ibuprofen administered systemically to combat adhesions.